Enhancing Localized Pesticide Action through Plant Foliage by Silver-Cellulose Hybrid Patches

Efficacy and efficiency of pesticide application in the field through the foliage still face many challenges. There exists a mismatch between the hydrophobic character of the leaf and the active molecule, low dispersion of the pesticides on the leaves' surface, runoff loss, and rolling down of the active molecules to the field, decreasing their efficacy and increasing their accumulation to the soil. We produced bacterial cellulose-silver nanoparticles (BC-AgNPs) hybrid patches by in situ thermal reduction under microwave irradiation in a scalable manner and obtaining AgNPs strongly anchored to the BC. Those hybrids increase the interaction of the pesticide (AgNPs) with the foliage and avoids runoff loss and rolling down of the nanoparticles. The positive antibacterial and antifungal properties were assessed in vitro against the bacteria Escherichia coli and two agro-economically relevant pathogens: the bacterium Pseudomonas syringae and the fungus Botrytis cinerea. We showed in vivo inhibition of the infection in Nicotiana benthamiana and tomato leaves, as proven by the suppression of the expression of defense molecular markers and reactive oxygen species production. The hydrogel-like character of the bacterial cellulose matrix increases the adherence to the foliage of the patches

ATR is required to complete meiotic recombination in mice

Precise execution of recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated resected DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of recombination markers on unsynapsed axes during meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian meiotic recombination.We thank M. A. Handel (The Jackson Laboratory, Bar Harbor, USA) for the anti-H1T antibody; E. Marcon for the anti-RPA antibody (University of Toronto, Canada); A. Toth for the anti-pHORMAD2 antibody (U. Dresden, Germany) and N. Hunter for the anti- RNF212 antibody (UC Davis, USA); J. Turner (National Institute for Medical Research,London, UK) for assistance in the RNA-FISH experiments, for the X chromosome probe,for providing AtrFL/−testis samples and for sharing unpublished data; L. Kauppi(University of Helsinki, Finland) for providing us with protocols for the testis cultures;and members of the Roig lab and the Spanish Ministerio de Ciencia e Innovación-funded Network of Spanish groups working on Meiosis (MeioNet, BFU201‐71786‐REDT) and Enrique Martínez Pérez (Imperial College, London, UK) for helpful discussions. M.M.O. was supported by a FPI fellowship from the Ministerio de Ciencia e Innovación (BES-2011-045381). J.L. was supported in part by American Cancer Society post-doctoral fellowship (PF-12-157-01-DMC). S.K. is an Investigator of the Howard Hughes Medical Institute. This work was supported by the Ministerio de Ciencia e Innovación (BFU2010-18965, BFU2013-43965-P and BFU2016-80370-P, I.R.), by the UAB-Aposta award to young investigators (APOSTA2011-03, I.R.) and by the NIH (R35 GM118175, to M.J.and R35 GM118092 to S.K.).S

ATR is required to complete meiotic recombination in mice

Precise execution of recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated resected DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of recombination markers on unsynapsed axes during meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian meiotic recombination

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study

Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. None. [Abstract copyright: Copyright © 2023 Elsevier Ltd. All rights reserved.

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population